Dopamine and schizophrenia-a cortically corrective perspective

The traditional dopamine hypothesis holds that excessive striatal/limbic dopamine-mediated transmission is causally related to the pathophysiology of schizophenia. However, schizophrenia is not cured by dopamine blocking drugs and is associated with relatively few replicable, direct indices of dopamine-mediated dysregulation. In comparison, the evidence supporting limbic and neocortical abnormalities in schizophrenia is robust. In light of what is known about these cortical abnormalities and about brain development and connectivity, the overall research data point to an early pathological process affecting temporal-limbic and/or prefrontal cortices which becomes clinically manifested later in life. To the extent that dopamine dysregulation may be a factor in the expression of some schizophrenic symptoms, it probably represents a secondary, 'downstream' effect of the cortical abnormalities. A number of possible mechanisms are described that might explain the relationship between cortical abnormalities and dopamine dysregulation in schizophrenia.